Mutans streptococci have been convincingly implicated in the initiation of dental caries in humans. The ability of these organisms to accumulate and colonize on the tooth surface has been associated with the synthesis of glucans from sucrose. Glucans are synthesized by constitutively secreted glucosyltransferase (GTF) enzymes. These enzymes have been considered as potential components of a dental caries vaccine because of their role in the pathogenicity of Mutans streptococci. However, vaccines based on intact GTF have a variety of disadvantages, such as the presence of inappropriate epitopes and excess molecular material that does not possess appropriate immunogenic features.
It is quite likely that protection against dental caries will involve functional inhibition of the catalytic and/or the glucan-binding activities of GTF. Epitopes associated with these functions would theoretically be primary targets for immunological attack, provided that the relevant sequences are located in molecular areas that are accessible to antibody. Subunit vaccines provide a method to block functional domains without inducing immunity to irrelevant or unwanted epitopes. It has been reported that synthetic peptide vaccines associated with catalytic or glucan-binding domains of GTF can protect rats from experimental dental caries (Taubman et al., Infect. Immun. 63:3088–3093 (1995)). One of the peptides that was successfully used as a vaccine (Smith et al., Infect. Immun. 62:5470–5476 (1994)) demonstrated a sequence containing an aspartic acid (aspartate 451 in S. mutans GTF-B) to which the glucosyl moiety of sucrose was covalently bound (Mooser et al., J. Biol. Chem. 266:8916–8922 (1991)).